Exploiting the Fungus Among Us

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Exploiting the Fungus Among Us

Researchers said on Sunday they had developed a way to use yeast to screen drugs to see how they work, and said it might offer a cheap and easy test for developing new drugs.

The method, developed by a team at Stanford University, could offer a quick and accurate way to screen compounds to fight cancer, new antibiotics, and other drugs, the researchers said.

"It's obviously very easy to test on yeast," said Dr. Guri Giaever, a Stanford biochemist who worked on the study. "It could be a preclinical test before animal studies are done."

Yeast are useful for testing human drugs because many of their genes are very similar to ours. "About 50 percent of all yeast genes have some homology to a human gene," Giaever said.

Scientists do not understand how many common drugs actually work. Although aspirin has been used for decades, researchers only discovered in recent years how it works – by inhibiting enzymes known as COX-1 and COX-2.

As scientists learn more and more about human genes, companies hope to find key genes and tailor drugs to specifically affect them.

But Giaever's team offers a method that takes just the opposite tack – taking a drug and finding the gene, or genes, that it affects.

Writing in the journal Nature Genetics, the team said they developed 200 different strains of the brewer's yeast Saccharomyces cerevisiae. It was the first living organism whose complete genome was sequenced, and scientists have been collaborating for years to know about half its 6,000 genes.

Like humans, yeast inherit two copies of each gene. In humans, other animals, and plants, one copy is inherited from each parent, and usually an organism functions just fine with one working copy.

For some genes, however, the loss of one copy weakens the organism.

Giaever's team knocked out one copy of each of 200 different genes in their yeast. They then tested the weakened yeast against drugs.

For their experiment, they chose drugs with known gene targets. For instance, the antibiotic tunicamycin is known to affect a gene known as ALG7, which is important for cell growth.

As expected, when the weakened yeast were grown in culture with the drugs, they did poorly.

The idea is now to knock out genes one by one and test the yeast against drugs that do not have a known genetic target – drugs that work, but whose mechanism is not known.

Gaiever said the yeast experiments would be ideally suited for testing cancer drugs. He also said they could be used to screen drugs to find out why they cause certain side effects.